Chinese hamsters are noted for having genetic diabetes mellitus of the non-obese, insulin-deficient type. To better define the mechanisms which control the release of hormones from the Islet of Langerhans, the pancreases of several different sublines of diabetic Chinese hamster will be perfused in vitro with a variety of secretagogue and the release of insulin, glucagon, and somatostatin will be measured. Because the time (age) of onset of glucosuria is well-defined in highly-inbred sublines, animals can be identified in the pre-diabetic stage. Young animals' pancreases will be perfused to determine the age of onset and progression of abnormalities in the release of each hormone from the pre-diabetic stage on through overt diabetes. Genetically normal Chinese hamsters will serve as controls. To determine if correction of plasma glucose with exogenous insulin can allow the pancreas to "recover" its own endogenous insulin secretion, animals will receive continuous infusions of insulin (via multiple 2-week minipumps) prior to pancreas perfusion. The role of calcium in the control of membrance potential and insulin release will be studied by determining the minimum threshold (of Ca) necessary for glucose-stimulated insulin release and the level of increase which suppresses insulin release (presumably via increased Ca-activated K-permeability).